Pharmacokinetics of valsartan in patients with liver disease

Brookman, L.; Rolan, Paul; Benjamin, I. S.; Palmer, K R; Wyld, Peter; Lloyd, Peter; Flesch, G.; Waldmeier, Felix; Sioufi, A.; Mullins, Frank G. P.

doi:10.1016/s0009-9236(97)90029-1

Cited by 86 publications

(67 citation statements)

References 9 publications

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“…14,15 In patients with mild to moderate hepatic disease, a two-fold increase in AUC is observed and the t . is prolonged, 14,15,156 but, no dosage adjustment is needed in such patients. 14,15 No pharmacokinetic data are available in patients with severe hepatic diseases.…”

Section: S79mentioning

confidence: 99%

Clinical pharmacokinetics of angiotensin II (AT1) receptor blockers in hypertension

2000

J Hum Hypertens

284

215

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Angiotensin II receptor blockers (ARBs) represent a new class of effective and well tolerated orally active antihypertensive agents. Recent clinical trials have shown the added benefits of ARBs in hypertensive patients (reduction in left ventricular hypertrophy, improvement in diastolic function, decrease in ventricular arrhythmias, reduction in microalbuminuria, and improvement in renal function), and cardioprotective effect in patients with heart failure. Several large long-term studies are in progress to assess the beneficial effects of ARBs on cardiac hypertrophy, renal function, and cardiovascular and cerebrovascular morbidity and mortality in hypertensive patients with or without diabetes mellitus, and the value of these drugs in patients with heart disease and diabetic nephropathy.The ARBs specifically block the interaction of angiotensin II at the AT 1 receptor, thereby relaxing smooth muscle, increasing salt and water excretion, reducing plasma volume, and decreasing cellular hypertrophy. These agents exert their blood pressure-lowering effect mainly by reducing peripheral vascular resistance usually without a rise in heart rate. Most of the commercially available ARBs control blood pressure for 24 h after once daily dosing. Sustained efficacy of blood pressure control, without any evidence of tachyphylaxis, has been demonstrated after long-term administration (3 years) of some of the ARBs. The efficacy of ARBs is similar to that of thiazide diuretics, beta-blockers, angiotensin-converting enzyme inhibitors or calcium channel blockers in patients with similar degree of hypertension. Higher daily doses, dietary salt restriction, and concomitant diuretic or ACE inhibitor administration amplify the antihypertensive effect of ARBs. The ARBs have a low incidence of adverse effects (headache, upper respiratory infection, back pain, muscle cramps, fatigue and dizziness), even in the elderly patients. After the approval of losartan, five other ARBs (candesartan cilexetil, eprosartan, irbesartan, telmisartan, and valsartan) and three combinations with hydrochlorothiazide (irbesartan, losartan and valsartan) have been approved as antihypertensive agents, and some 28 compounds are in various stages of development.The ARBs are non-peptide compounds with varied structures; some (candesartan, losartan, irbesartan, and valsartan) have a common tetrazolo-biphenyl structure. Except for irbesartan, all active ARBs have a carboxylic acid group. Candesartan cilexetil is a prodrug, while losartan has a metabolite (EXP3174) which is more active than the parent drug. No other metabolites of ARBs contribute significantly to the antihypertensive effect.Keywords: angiotensin receptor blockers; candesartan; eprosartan; irbesartan; losartan; telmisartan; valsartan; pharmacokinetics After oral administration, the ARBs are rapidly absorbed (time for peak plasma levels ‫؍‬ 0.5-4 h) but they have a wide range of bioavailability (from a low of 13% for eprosartan to a high of 60-80% for irbesartan); food does not influence the bioavaila...

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Section: S79mentioning

confidence: 99%

Clinical pharmacokinetics of angiotensin II (AT1) receptor blockers in hypertension

2000

J Hum Hypertens

284

215

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“…It has been reported that lisinopril and quinapril hydrochloride are primarily eliminated in urine and that valsartan is not eliminated in urine (9)(10)(11).…”

Section: Discussionmentioning

confidence: 99%

“…It has also been reported that lisinopril has a poor ability to bind to plasma protein and that quinapril hydrochloride and valsartan have a good ability to bind to plasma protein (9)(10)(11) and it has been shown that the halflife of lisinopril is longer than that of quinapril hydrochloride (9,10). We accordingly thought that lisinopril had a greater potential to induce adverse effects, such as angioedema, than did quinapril hydrochloride in the present case with severe renal impairment, because increased bradykinin levels appear to be one of the mechanisms underlying the development of ACE-I-associated angioedema.…”

Section: Discussionmentioning

confidence: 99%

Drug-induced Isolated Visceral Angioneurotic Edema

et al. 2005

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A 44-year-old woman on maintenance hemodialysis was admitted to our hospital because of severe abdominal pain. The patient had been medicated with lisinopril and valsartan for hypertension for one month prior to admission. An abdominal computerized scan (CT) showed a dilated and thickened loop of the small bowel with massive ascites and a small nodule in the jejunum. The patient's abdominal pain was thought to be due to isolated visceral angioneurotic edema induced by lisinopril and/or valsartan, and medication of these two drugs was therefore stopped. Her symptoms resolved and an abdominal CT demonstrated almost complete resolution of ascites and of small bowel edema except for a small nodule in the jejunum. A laparoscopic operation was performed to excise the small nodule of the jejunum, and a histological diagnosis of accessory pancreas of the jejunum was made. This is the first report of isolated visceral angioneurotic edema induced by lisinopril and/or valsartan in a patient on maintenance hemodialysis and, moreover, with the association of accessory pancreas of the jejunum.

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“…Hepatic clearance is the primary route of elimination of valsartan (*83% of the dose) [37,99] and contributes to the clearance of sacubitril (37-48% of the dose; primarily as sacubitrilat). Compared with healthy subjects, in patients with mild and moderate hepatic impairment, AUCs increased by 1.5-and 3.4-fold for sacubitril, by 1.5-and 1.9-fold for sacubitrilat, and by 1.2-and 2.1-fold for valsartan, respectively [45].…”

Section: Patients With Hepatic Impairmentmentioning

confidence: 99%

Erratum to: Clinical Pharmacokinetics of Sacubitril/Valsartan (LCZ696): A Novel Angiotensin Receptor–Neprilysin Inhibitor

et al. 2017

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Sacubitril/valsartan (LCZ696) is indicated for the treatment of heart failure with reduced ejection fraction. Absorption of sacubitril/valsartan and conversion of sacubitril (prodrug) to sacubitrilat (neprilysin inhibitor) was rapid with maximum plasma concentrations of sacubitril, sacubitrilat, and valsartan (angiotensin receptor blocker) reaching within 0.5, 1.5-2.0, and 2.0-3.0 h, respectively. With a twofold increase in dose, an increase in the area under the plasma concentration-time curve was proportional for sacubitril, *1.9-fold for sacubitrilat, and *1.7-fold for valsartan in healthy subjects. Following multiple twice-daily administration, steady-state maximum plasma concentration was reached within 3 days, showing no accumulation for sacubitril and valsartan, while *1.6-fold accumulation for sacubitrilat. Sacubitril is eliminated predominantly as sacubitrilat through the kidney; valsartan is eliminated mainly by biliary route. Drug-drug interactions of sacubitril/valsartan were evaluated with medications commonly used in patients with heart failure including furosemide, warfarin, digoxin, carvedilol, levonorgestrel/ethinyl estradiol combination, amlodipine, omeprazole, hydrochlorothiazide, intravenous nitrates, metformin, statins, and sildenafil. Co-administration with sacubitril/valsartan increased the maximum plasma concentration (*2.0-fold) and area under the plasma concentration-time curve (1.3-fold) of atorvastatin; however, it did not affect the pharmacokinetics of simvastatin. Age, sex, or ethnicity did not affect the pharmacokinetics of sacubitril/valsartan. In patients with heart failure vs. healthy subjects, area under the plasma concentration-time curves of sacubitril, sacubitrilat, and valsartan were higher by approximately 1.6-, 2.1-, and 2.3-fold, respectively. Renal impairment had no significant impact on sacubitril and valsartan area under the plasma concentration-time curves, while the area under the plasma concentrationtime curve of sacubitrilat correlated with degree of renal function (1.3-, 2.3-, 2.9-, and 3.3-fold with mild, moderate, and severe renal impairment, and end-stage renal disease, respectively). Moderate hepatic impairment increased the area under the plasma concentration-time curves of valsartan and sacubitrilat *2.1-fold.The in-text citations in the tables were misaligned with the references in the original article. The full article with all the corrections is republished here.The online version of the original article can be found under

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Pharmacokinetics of valsartan in patients with liver disease

Abstract: These data are consistent with the pharmacokinetics of valsartan in that biliary excretion is the main route of elimination.

Cited by 86 publications

References 9 publications

Clinical pharmacokinetics of angiotensin II (AT1) receptor blockers in hypertension

Clinical pharmacokinetics of angiotensin II (AT1) receptor blockers in hypertension

Drug-induced Isolated Visceral Angioneurotic Edema

Erratum to: Clinical Pharmacokinetics of Sacubitril/Valsartan (LCZ696): A Novel Angiotensin Receptor–Neprilysin Inhibitor

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